Abstract
Purpose. For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). Materials and Methods. The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. Results. The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. Conclusion. The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.
| Original language | English |
|---|---|
| Pages (from-to) | 2924-2936 |
| Number of pages | 13 |
| Journal | Pharmaceutical Research |
| Volume | 25 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2008 |
| Externally published | Yes |
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Keywords
- Gene delivery
- PEG
- Polyplex micelle
- TGF-β inhibitor
- Triblock copolymer
ASJC Scopus subject areas
- Pharmaceutical Science
- Organic Chemistry
- Molecular Medicine
- Pharmacology (medical)
- Biotechnology
- Pharmacology
Cite this
Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue. / Miyata, Kanjiro; Oba, Makoto; Kano, Mitsunobu; Fukushima, Shigeto; Vachutinsky, Yelena; Han, Muri; Koyama, Hiroyuki; Miyazono, Kohei; Nishiyama, Nobuhiro; Kataoka, Kazunori.
In: Pharmaceutical Research, Vol. 25, No. 12, 12.2008, p. 2924-2936.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue
AU - Miyata, Kanjiro
AU - Oba, Makoto
AU - Kano, Mitsunobu
AU - Fukushima, Shigeto
AU - Vachutinsky, Yelena
AU - Han, Muri
AU - Koyama, Hiroyuki
AU - Miyazono, Kohei
AU - Nishiyama, Nobuhiro
AU - Kataoka, Kazunori
PY - 2008/12
Y1 - 2008/12
N2 - Purpose. For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). Materials and Methods. The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. Results. The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. Conclusion. The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.
AB - Purpose. For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). Materials and Methods. The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. Results. The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. Conclusion. The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.
KW - Gene delivery
KW - PEG
KW - Polyplex micelle
KW - TGF-β inhibitor
KW - Triblock copolymer
UR - http://www.scopus.com/inward/record.url?scp=57149133401&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57149133401&partnerID=8YFLogxK
U2 - 10.1007/s11095-008-9720-2
DO - 10.1007/s11095-008-9720-2
M3 - Article
C2 - 18781378
AN - SCOPUS:57149133401
VL - 25
SP - 2924
EP - 2936
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
IS - 12
ER -